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Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status

Withdrawn

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Radium-223 dichloride (Xofigo, BAY88-8223)

Placebo

Bortezomib

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Radium-223 dichloride, bortezomib, dexamethasone, early relapsed multiple myeloma, combination therapy multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Cytologically or histologically confirmed diagnosis of multiple myeloma
Subjects must have received at least 1 and not more than 3 previous lines of treatment and have had a response to treatment (i.e., achieved a minimal response [MR] or better) according to the International Myeloma Working Group (IMWG) uniform response criteria
Subjects must have had progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment
Subjects must have measurable disease defined as at least 1 of the following (according to central laboratory results):
- Serum M-protein ≥1 g/dL
- Urine M-protein ≥200 mg/24 hours
- Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio
≥1 bone lesion identifiable by radiograph, computed tomography, magnetic resonance imaging, or bone scintigraphy
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
Subjects must be nonrefractory to bortezomib and had no progression during or within 60 days after completion of bortezomib
Absolute neutrophil count (ANC) ≥1.5 × 10e9/L, hemoglobin (Hb) ≥9.0 g/dL, and platelet count ≥75.0 × 10e9/L independent of transfusion of red blood cells (RBC) or platelet concentrates and independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF)

Exclusion Criteria:

Systemic glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 4 weeks prior to first dose, unless tapered and on a stable dose ≤10 mg/day for at least 1 week
Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light chain (AL) amyloidosis
Plasma cell leukemia
Systemic anti-cancer therapy within 4 weeks prior to first dose
Radiation therapy in the previous 4 weeks prior to first dose except if given for pain management and involves less than 10% of the bone marrow
Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical
Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic cardiac ischemia, cardiomyopathy, clinically relevant ventricular arrhythmia, pericardial disease, unstable angina or myocardial infarct in the previous 6 months prior to first dose, left ventricular ejection fraction <40%
Neuropathy ≥ Grade 2 or Grade 1 with pain

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Radium-223 dichloride [Phase 1, dose 1]

Radium-223 dichloride [Phase 1, dose 2]

Radium-223 dichloride [Phase 1, dose 3]

Placebo +SoC [Phase 2]

Radium-223 dichloride + SoC [Phase 2]

Arm Description

Phase 1: Radium-223 dichloride; 30 kiloBecquerel (kBq)/kg body weight (33 kBq/kg after implementation of National Institute of Standards and Technology [NIST] update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Phase 1: Radium-223 dichloride; 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Phase 1: Radium-223 dichloride; 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Phase 2: Matching placebo (isotonic saline) every 4 weeks for a total of 6 doses plus SoC (Standard of care) bortezomib/dexamethasone.

Phase 2: Phase 1b-selected dose of radium-223 dichloride every 4 weeks for 6 doses plus SOC bortezomib/dexamethasone

Outcomes

Primary Outcome Measures

Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)

Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression

Secondary Outcome Measures

Objective response rate (ORR) in Phase 1b, in the proportion of subjects in the analysis population who have complete response (CR), stringent complete response (sCR), very good partial response (VGPR), partial response (PR), or stable disease (SD)

Duration of response in Phase 1b, defined as the time (in days) from the date of first response to treatment (CR, sCR, VGPR, PR) to the date of disease progression or death

Number of participants with adverse events in phase 2

Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause

Time to Symptomatic Skeletal Event (SSE) in Phase 2, defined as the time (days) from the date of randomization to the date of the first on-study SSE

Symptomatic skeletal event free survival in Phase 2, defined as the time from randomization to the occurrence of 1 of the following: First on-study SSE or Death from any cause if death occurs before a documented SSE

Time to pain progression in Phase 2

Duration of response in Phase 2

Objective Response Rate (ORR) in Phase 2

Full Information

NCT ID

NCT02605356

First Posted

November 12, 2015

Last Updated

October 6, 2016

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT02605356

Brief Title

Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma

Official Title

A Phase 1b/2 Trial to Evaluate the Safety and Efficacy of Radium-223 Dichloride (BAY88-8223) in Combination With Bortezomib and Dexamethasone in Early Relapsed Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Withdrawn

Why Stopped

Study restarted under new study number 18987

Study Start Date

October 2016 (undefined)

Primary Completion Date

November 2019 (Anticipated)

Study Completion Date

July 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study will be conducted in 2 parts. The phase 1b part will be an international, phase 1b, open-label, dose-escalation assessment of radium-223 dichloride administered with bortezomib and dexamethasone in subjects with relapsed multiple myeloma. The primary endpoint of the phase 1b part is to determine the optimal dose of radium-223 dichloride in combination with bortezomib/dexamethasone for the Phase 2 portion of the study. The phase 2 part will be an international, phase 2, double-blind, randomized, placebo-controlled assessment of radium-223 dichloride versus placebo administered with bortezomib and dexamethasone, in subjects with relapsed multiple myeloma. Randomization (1:1) in the phase 2 part will be stratified by: Prior bortezomib treatment (yes, no) Prior treatment (1 prior line of treatment, >1 prior line of treatment) Approximately 30 subjects (10 subjects per cohort) will be enrolled in the phase 1b part of the study and approximately 196 subjects will be enrolled in the phase 2 part of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

Radium-223 dichloride, bortezomib, dexamethasone, early relapsed multiple myeloma, combination therapy multiple myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Radium-223 dichloride [Phase 1, dose 1]

Arm Type

Experimental

Arm Description

Arm Title

Radium-223 dichloride [Phase 1, dose 2]

Arm Type

Experimental

Arm Description

Phase 1: Radium-223 dichloride; 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Arm Title

Radium-223 dichloride [Phase 1, dose 3]

Arm Type

Experimental

Arm Description

Phase 1: Radium-223 dichloride; 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Arm Title

Placebo +SoC [Phase 2]

Arm Type

Placebo Comparator

Arm Description

Phase 2: Matching placebo (isotonic saline) every 4 weeks for a total of 6 doses plus SoC (Standard of care) bortezomib/dexamethasone.

Arm Title

Radium-223 dichloride + SoC [Phase 2]

Arm Type

Experimental

Arm Description

Phase 2: Phase 1b-selected dose of radium-223 dichloride every 4 weeks for 6 doses plus SOC bortezomib/dexamethasone

Intervention Type

Drug

Intervention Name(s)

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Primary Outcome Measure Information:

Title

Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)

Time Frame

At 13 months

Title

Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression

Time Frame

Up to 25 months

Secondary Outcome Measure Information:

Title

Time Frame

Approximately 12 months

Title

Duration of response in Phase 1b, defined as the time (in days) from the date of first response to treatment (CR, sCR, VGPR, PR) to the date of disease progression or death

Time Frame

Approximately 12 months

Title

Number of participants with adverse events in phase 2

Time Frame

Up to 25 months

Title

Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause

Time Frame

Up to 25 months

Title

Time to Symptomatic Skeletal Event (SSE) in Phase 2, defined as the time (days) from the date of randomization to the date of the first on-study SSE

Time Frame

Up to 25 months

Title

Time Frame

Up to 25 months

Title

Time to pain progression in Phase 2

Time Frame

Up to 25 months

Title

Duration of response in Phase 2

Time Frame

Up to 25 months

Title

Objective Response Rate (ORR) in Phase 2

Time Frame

Up to 25 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Cytologically or histologically confirmed diagnosis of multiple myeloma Subjects must have received at least 1 and not more than 3 previous lines of treatment and have had a response to treatment (i.e., achieved a minimal response [MR] or better) according to the International Myeloma Working Group (IMWG) uniform response criteria Subjects must have had progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment Subjects must have measurable disease defined as at least 1 of the following (according to central laboratory results): Serum M-protein ≥1 g/dL Urine M-protein ≥200 mg/24 hours Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio ≥1 bone lesion identifiable by radiograph, computed tomography, magnetic resonance imaging, or bone scintigraphy Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 Subjects must be nonrefractory to bortezomib and had no progression during or within 60 days after completion of bortezomib Absolute neutrophil count (ANC) ≥1.5 × 10e9/L, hemoglobin (Hb) ≥9.0 g/dL, and platelet count ≥75.0 × 10e9/L independent of transfusion of red blood cells (RBC) or platelet concentrates and independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) Exclusion Criteria: Systemic glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 4 weeks prior to first dose, unless tapered and on a stable dose ≤10 mg/day for at least 1 week Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light chain (AL) amyloidosis Plasma cell leukemia Systemic anti-cancer therapy within 4 weeks prior to first dose Radiation therapy in the previous 4 weeks prior to first dose except if given for pain management and involves less than 10% of the bone marrow Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic cardiac ischemia, cardiomyopathy, clinically relevant ventricular arrhythmia, pericardial disease, unstable angina or myocardial infarct in the previous 6 months prior to first dose, left ventricular ejection fraction <40% Neuropathy ≥ Grade 2 or Grade 1 with pain

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259-5404

Country

United States

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

City

Encinitas

State/Province

California

ZIP/Postal Code

92024

Country

United States

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70006

Country

United States

City

Rockville

State/Province

Maryland

ZIP/Postal Code

20850-6535

Country

United States

City

New York

State/Province

New York

ZIP/Postal Code

10032-3729

Country

United States

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

City

Watertown

State/Province

South Dakota

ZIP/Postal Code

57201

Country

United States

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

City

Box Hill

ZIP/Postal Code

3128

Country

Australia

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

City

Bruxelles - Brussel

ZIP/Postal Code

1090

Country

Belgium

City

Bruxelles - Brussel

ZIP/Postal Code

1200

Country

Belgium

City

Liege

ZIP/Postal Code

4000

Country

Belgium

City

Yvoir

ZIP/Postal Code

5530

Country

Belgium

City

Quebec

ZIP/Postal Code

G1R 2J6

Country

Canada

City

Tübingen

State/Province

Baden-Württemberg

ZIP/Postal Code

72076

Country

Germany

City

München

State/Province

Bayern

ZIP/Postal Code

81377

Country

Germany

City

Mainz

State/Province

Rheinland-Pfalz

ZIP/Postal Code

55131

Country

Germany

City

Berlin

ZIP/Postal Code

12203

Country

Germany

City

Athens

ZIP/Postal Code

11528

Country

Greece

City

Rio / Patra

ZIP/Postal Code

26500

Country

Greece

City

Afula

ZIP/Postal Code

1834111

Country

Israel

City

Haifa

ZIP/Postal Code

31048

Country

Israel

City

Jerusalem

ZIP/Postal Code

9112001

Country

Israel

City

Ramat Gan

ZIP/Postal Code

5262000

Country

Israel

City

Zerifin

ZIP/Postal Code

6093000

Country

Israel

City

Bologna

State/Province

Emilia-Romagna

ZIP/Postal Code

40138

Country

Italy

City

Reggio Emilia

State/Province

Emilia-Romagna

ZIP/Postal Code

42123

Country

Italy

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20089

Country

Italy

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20132

Country

Italy

City

Novara

State/Province

Piemonte

ZIP/Postal Code

28100

Country

Italy

City

Torino

State/Province

Piemonte

ZIP/Postal Code

10126

Country

Italy

City

Cagliari

State/Province

Sardegna

ZIP/Postal Code

09121

Country

Italy

City

Firenze

State/Province

Toscana

ZIP/Postal Code

50141

Country

Italy

City

Pisa

State/Province

Toscana

ZIP/Postal Code

56126

Country

Italy

City

Goyang-si

State/Province

Gyeonggido

ZIP/Postal Code

410-769

Country

Korea, Republic of

City

Daegu

ZIP/Postal Code

700-701

Country

Korea, Republic of

City

Jeollanam-do

ZIP/Postal Code

519-763

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

137-701

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

City

Badalona

State/Province

Barcelona

ZIP/Postal Code

08916

Country

Spain

City

San Sebastián

State/Province

Guipúzcoa

ZIP/Postal Code

20014

Country

Spain

City

Palma de Mallorca

State/Province

Illes Baleares

ZIP/Postal Code

07010

Country

Spain

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

City

Madrid

ZIP/Postal Code

28006

Country

Spain

City

Madrid

ZIP/Postal Code

28046

Country

Spain

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

City

Valencia

ZIP/Postal Code

46017

Country

Spain

City

Taichung

ZIP/Postal Code

40447

Country

Taiwan

City

Taipei

ZIP/Postal Code

10016

Country

Taiwan

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

City

Taipei

Country

Taiwan

12. IPD Sharing Statement

Learn more about this trial

Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma

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